Cloning and expression of the gene involved in Sanfilippo B syndrome (mucopolysaccharidosis III B)

Sanfilippo B syndrome is caused by a deficiency of alpha-N- acetylglucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulphate. Accumulation of the substrate in lysosomes results in degeneration of the central nervous system with progressive dementia often combined with hyperactivity and aggressive behaviour. In order to clone the deficient gene, we purified the enzyme from human placenta and obtained amino acid sequence information. Alignment of one of the CNBr generated internal peptides to sequence from the database revealed the chromosomal location of the gene in the 5' upstream flanking region of the gene for 17-beta-hydroxysteroid-dehydrogenase at 17q21.1. The available DNA sequence was used to clone the cDNA coding for alpha-N- acetylglucosaminidase and analyse its gene structure. The gene is fully contained in the 5' upstream flanking region of the gene for 17-beta- hydroxysteroid-dehydrogenase and interrupted by five introns. The cDNA clone has a length of 2575 bp and encodes a protein of 743 amino acids. Chinese hamster ovary cells transfected with the cDNA construct show alpha-N-acetylglucosaminidase activity about 17-fold over background. This will allow correction studies with NAG deficient Sanfilippo B cell lines and facilitate the development of enzyme replacement therapy for these patients.      

Paramagnetic macrocyclic complexes as contrast agents for MR imaging: proton nuclear relaxation rate enhancement in aqueous solution and in rat tissues

Paramagnetic macrocyclic chelates show promise as magnetic resonance (MR) imaging contrast agents due to stability and relaxivity comparable to those of DTPA-type chelates. For the three copper and manganese macrocyclic complexes studied in aqueous solution, T1 and T2 relaxivities ranged from 0.14 to 5.88 mM-1sec-1 at 6.25 MHz. In rats, the intravenous administration of 16 mumol/kg of Mn(cyclam) caused the liver T1 relaxation rate to double at 15 minutes after injection. T1 measurements by pulsed MR imaging and manganese analyses on excised tissue showed that both relaxation rate (1/T1) and manganese content of liver and kidney increase linearly with the dosage of Mn(cyclam). The linear relationship between 1/T1 and manganese content can be considered an "in tissue" relaxivity plot for the agent. The resulting relaxivity is 54 mM-1sec-1 in liver, compared with 3.1 mM-1sec-1 in aqueous solution. Although this work is preliminary, the implication for medical MR imaging applications is that macrocyclic contrast agents can be effective at approximately one-tenth the current typical dose used for gadolinium DTPA.     

Alterations in sensitivity to nonspecific cell-mediated lysis associated with tumor progression: characterization of activated macrophage- and natural killer cell-resistant tumor variants

Certain "membrane-mutant," lectin-resistant (Lecr) variants derived from the highly metastatic and poorly immunogenic DBA/2 mouse tumor MDAY-D2 previously were found to differ substantially in their ability to grow and to metastasize. In the present study, the parental MDAY-D2 tumor and several wheat germ agglutinin-resistant (WGAr) variants were examined for alterations in sensitivity to activated macrophage (M phi)- and natural killer cell (NK)-mediated lysis. The results indicated that selection in WGA after mutagenic treatment of a metastatic parental tumor cell line (MDAY-D2), which was M phi-sensitive (M phi S) and NK-resistant (NKR), can result in the isolation of a significantly M phi-resistant (M phi R) and NK-sensitive (NKS) tumor variant, MDW4. The in vivo hybridization of the M phi R, NKS, Lecr MDW4 variant with a normal host-derived cell within a primary subcutaneous tumor, previously demonstrated to result in the progressive and selective outgrowth and metastasis of hybrid products, was found to be associated directly with reversion to the M phi S, NKR phenotype of the metastatic parental MDAY-D2 cell line. DMA/2 mice given iv injections of 10(5) M phi R, NKS cells (MDW4 or MDW4-110c1, a cloned line isolated from a subcutaneous primary tumor of an MDW4-injected animal) survived for a significantly prolonged period as compared to animals given injections of either the parental tumor or M phi S, NKR hybrid products isolated from a MDW4 subcutaneous primary tumor (MDW4-110c2) or visceral metastases (MDW4-24a, MDW4-24b, and MDW4-24c). The results clearly indicate an inverse relationship among the tumor variants in their ability to be lysed by either M phi or NK and suggest a central role for NK rather than M phi surveillance in this tumor system.     

海南省大劣按蚊实验室自然交配的驯化研究

目的 建立实验室大劣按蚊自然交配繁殖种群,为同类研究提供依据。方法 将野外捕捉并在实验室人工交配繁殖至第61代的大劣按蚊,按不同雌雄比例先后顺序置于大、中、小三种不同型号的蚊笼中喂养、驯化、观察产卵情况并计算产卵数和孵化率。结果 在大、中、小蚊笼内的分别驯化至第15、10和18代时成蚊卵的孵化率各达到82％、83．4％和80．7％,成功建立小蚊笼自然交配的大劣按蚊种群。结论 经实验室驯化的大劣按蚊能够自然交配、产卵、繁殖,有助于建立实验室自然种群。     

甲状腺机能亢进症危险因素病例对照研究

目的 探讨各危险因素与甲亢的关系。方法 对三亚地区110例甲亢采用1：2配比的病例对照研究,资料处理采用条件Logistic回归分析.结果 甲亢发病与下列5因素关系密切：家庭年收入(OR=2．055)、食用碘盐(OR=2．133)、喜食海产品(OR=2．183)、感染(OR=2．382)、家庭生活事件(OR=3．017) 结论 家庭生活事件、感染、喜食海产品、食用碘盐、家庭年收入增高等是甲亢的危险因素。     

海南省性罪错妇女11年性病感染情况调查分析

目的 通过对11年来性罪错人员性病感染情况的调查分析,掌握性病在性罪错妇女中流行的特点,为政府部门对性病防治政策的制定提供科学依据。方法 对1990年元月至2000年12月海南省妇女收容教育所被收教的性罪错妇女进行性病检查,统计其各种性病的发病人数,然后进行分析。结果 11年中共收教4780人,其中感染淋病、非淋菌性尿道炎(宫颈炎)、尖锐湿疣、梅毒、生殖器疱疹、HIV共2967例,阳性率为62．07％,其中非淋菌性尿道炎(宫颈炎)1826例(38．20％)、淋病469例(9、81％)、梅毒414例(8．7％)、尖锐湿疣246例(5．14％)、生殖器疱疹11例(0．23％)、HIV阳性1例(0．02%)。结论 性罪错妇女六种性病的患病率很高,达62．07％,其中非淋菌性尿道炎(宫颈炎)为其主要病种,淋病的患病率逐年下降,梅毒的患病率逐年上升,尖锐湿疣基本稳定,其流行特点值得我们重视。     

Surgeons' assessment of symptoms suggesting extrathoracic metastases in patients with lung cancer. Canadian Lung Oncology Group.

BACKGROUND: In patients with apparently operable non-small cell lung cancer (NSCLC), clinicians often omit investigation for M disease in asymptomatic patients. Previous investigations have not specified in detail what is meant by "symptomatic," and this could differ between surgeons. We have investigated the extent to which surgeons' criteria differ for presence of symptoms. METHODS: Participating surgeons from seven centers, enrolled patients they judged "asymptomatic" in a randomized trial of investigational strategies for NSCLC. Patients completed a structured questionnaire describing symptoms of the central nervous system (CNS). In 685 patients, we documented CNS symptom recurrence after resectional surgery over 1 year of follow-up. RESULTS: Two centers enrolled only patients without even the mildest symptoms. Three centers took an intermediate approach, occasionally classifying patients with mild symptoms as "asymptomatic" and thus enrolling them in the trial. Two centers classified an appreciable number of patients with minimal symptoms, and occasionally with more than minimal symptoms, as "asymptomatic." Patients with even mild CNS symptoms were more likely to subsequently present with CNS metastases. CONCLUSIONS: Thoracic surgeons differ in their ideas of what may constitute the symptoms of M disease. Patients with structured questionnaire results that suggest symptoms of CNS disease are more likely to have CNS symptom recurrence after resectional surgery.     

Hypertension secondary to progressive vascular neurofibromatosis

A 4 year old girl with neurofibromatosis type 1 (NF1) was referred for hypertension. An aortogram showed narrowing of the left main renal artery. An angiogram three and a half years later showed coarctation of the abdominal aorta. She underwent aortoplasty but the stenosis recurred. Vascular involvement in NF1 may be progressive and requires long term follow up.     

The “Glass” Stage: the Communicube

The transparent structures of the Communicube and Communiwell are described including their invention, practical uses, relevant theory and background.